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67 Cards in this Set

  • Front
  • Back
List two genus groups of Parvoviridae family and include a disease for each.
Erythrovirus (B19)
(Pathogenic to humans)

Dependovirus (AAV - Adeno-associated virus)
Parvovirus unique properties:

- size
- capsid
- envelope
- genome structure
Smallest DNA virus

Icosahedral

NO envelope

Single stranded DNA
What does parvovirus require for replication?
Mitotically active cells
Parvovirus generates _______ DNA strand during the ______ phase.
Complementary

S
For parvoviruses, what is required for viral transcription and replication?
Double stranded DNA
During parvovirus replication, the strand packaged into virions is plus or minus?

Which one has ALL genes on it?
Can be either

Plus
In respect to the manifestation of symptoms, when does the contagious period occur?
Contagious period PRECEDES symptoms.
B19:

- transmission?
- population affected?
Respiratory droplets

Children <15 (50%)
Adults by 40 (65%)
Elderly (90%)
What causes the B19 to be resistant to inactivation?
Lacking an envelope
Describe the mechanism of Parvovirus spread in humans.
1. Infects upper respiratory tract (some replication)

2. Migrate to bone marrow
(replicates in erythroid precursors)

3. Viremia/Cytolysis

4. Migrate back to upper respiratory tract
(replication)
What are the biphasic stages of B19?

Which one is infectious?

Describe each.
Initial Febrile Stage (infectious)
- virus release in respiratory secretions
- viremia/cytolysis of erythroid precursors (causing erythroid production)
- Erythroid production stops in 1 week

Symptomatic stage (noninfectious)
- Immune-mediated
- Rash, arthralgia
List the clinical syndromes associated with the following population group:

- children
- adults
- immunodeficient pts
- fetus
- pts with increased destruction of erythrocytes
Mild flu-like illness
Erythema infectiosum (5th dz)

Mild flu-like illness
Arthropathy (polyarthritis)

Persistent anemia

Fetal loss (hydrops fetalis)
Congenital anemia

Transient aplastic crisis
What are the population groups most at risk for B19? x5
Pregnant women (fetal infection)

Immunocompromised pts

Parents of children with B19

Elementary school aged children

Sickle cell patients (aplastic crisis)
Erythema infectiosum:

- virus responsible
- population affected
- seasons involved
- symptom progression
B19

Children 4-15

Late winter to spring

Unremarkable prodrome
(asymptomatic/nonspecific)
Followed by distint rash
(slapped cheek appearance)
Spreads from cheeks to extremities.
For adults, what are the usual symptoms associated with B19? x2

Is this preceded by something?

Where are the symptoms located?
Arthralgia and Arthritis

Usually NOT preceded by rash

Hands, wrists, ankles, knees
In seroNEGATIVE pregnant women, what is the risk associated with B19 infection?

What is the name of the disease associated with this and what are the symptoms?

When is the risk highest
30% risk of placental infection

HYDROPS FETALIS (anemia and CHF)

2nd trimester
Patients with B19 infections that are also chronically hemolytic anemic (e.g.-sickle cell anemia) suffer what consequence?
Aplastic crisis
What do you use to diagnose B19 virus infection?
ELISA - parvo specific IgM or IgG

PCR/Hybridization - viral DNA
What is the treatment for B19 infecions?
No specific antiviral therapy.

Immune globulins
Anti-inflammatory drugs
Isolation of hospitalized pts
In normal hosts, B19 induced bone marrow replication causes what event? (something you can see in lab tests)

What causes this result?
Decrease in hemoglobin levels

Increase in erythrocyte production
What viral mechanism is responsible for aplastic crisis in pts with chronic hemolytic anemia?
Viral replication of erythroid precursors
AAV (dependovirus) requires a second "helper" what?
herpes virus or adenovirus
What are the symptoms associated with infection of AAV?
Asymptomatic
HPV:

- genome structure
double stranded circular DNA
Function of HPV proteins:

- E1
- E2
Binds DNA at ori and promotes viral DNA replication (and has helicase activity)

Binds DNA, helps E1, and activates viral mRNA synthesis
For HPV, describe the actions and results of the E6 protein.
Binds to p53, inducing its degradation.

Since p53 is the sensory protein responsible for cell arrest and apoptosis,

the result is NO arrest, and NO apoptosis.
For HPV, describe the action and results of the E7 protein.
E7 will interact with the pRb/E2F complex. This will cause the formation of the pRb/E7 complex and displace E2F.

E2F will then go and initiate transcription of S-phase genes

allowing for DNA replication
What are the L1 and L2 gene products in HPV?

When are they expressed
Structural (capsid) proteins

Expressed late
Papillomavirus only replicates in which part of the body?
Epidermis of skin an dmucosa.
Describe the life cycle of papillomavirus.
1. The virus first infects the basal cells (stratum germinativum)

2. Expression of early genes is low (for maintenance) and causes cell hypertrophy AND decreases differentiation.

3. As the virus-infected cells reach the Stratum Spinosum, genome amplification goes up markedly.

4. This is followed by late expression of L1 and L2 capsid proteins, which only occur in the upper layers.

5. New virions are created, then released with the dying cell.
Why does HPV like to infect the stratum germinativum (basal cells)?
Because these cells are mitotically active and can promote viral DNA replication.
Why does HPV genome replication increase at the stratum spinosum?
Because cells at this cell layer is not competent for DNA replication nor cell division.
Decrease in differentiation leads to _________ of the epithelium.

State the effects for the following following cell layers:

- S. corneum/lucideum
- S. granulosum
- S. spinosum
Hypertrophy

Hyperkeratosis
Parakeratosis
Akanthosis
What is a koilocyte?

How does it form?
Virus producing vacuolated cell.

Nucleus degenerates and large vacuole forms.
In HPV, the proteins _____ and _____ are oncogenes.

Their function is to initiate _______ in the ________ cells of the _________ cell layer.
E6
E7

viral DNA replication

quiescent

Spinosum
In HPV, what is the transcription factor that regulates the expression and repression of E6 and E7?
E2
What is required for the progression of HPV infection to HPV carcinoma?

Describe the mechanism.
It requires integration into the host chromosome.

This destroys the ORFs of E1 and E2. This leaves E6 and E7 unregulated, causing massive growth.
HPV pathogenesis is directly related to ___________ in which the virus ___________.
Replication strategy

stimulates cell growth
These are HPV benign outgrowths of cells.
Warts
Cervical cancer is a result of this type of mechanism occurring with HPV.
Cell transformation
What cell layer has the highest rate of viral DNA synthesis in HPV?

What cell layer has the highest layer of late gene expression?
Stratum Granulosum

Stratum Corneum
What is the most common (>90%) prognosis for HPV lesions?
Spontaneous regression.
Which HPV type is the most common STD in terms of seroprevalence?
HPV 33
List the types of HPV for the following:

- cutaneous warts
- epidermodysplasia verruciformis
- laryngeal papillomas
- condyloma acuminatum
- cervical neoplasia
HPV 1-4

HPV 5 & 8

HPV 6 & 11

HPV 6 & 11

HPV 16 & 18 (31,33,35,39,45)
HPV 16 is a "high risk" HPV type that is associated with CA of what?
Cervical, vaginal, penile, anal

Esophagus

Heand and Neck
HPV 18 is a "high risk" HPV type that is associated with what CA?
Adenocarcinoma
HPV cancers affect which gender more?

What is the most common HPV induced CA?
Women

Cervical
What are the risk factors for cervical cancer?
Smoking

Persistent infection

Infection with high risk HPV

Compromised immune system
What are the tests used to diagnose HPV? x2

List positive signs.
Microscope (hyperkeratosis)

Papanicolaou smear (koilocytosis)
HPV vaccine:

- contains what?
- useful against what types
- how effective?
- what about from cervical neoplasias?
L1 protein

HPV 16, 18

100%

>70% protection
What are the viruses associated with human polyomavirus? x4
BK

JC

KI

SV-40
SV-40:

- potent virus of what
- how widespread?
- etiology in tumors?
Potent DNA tumor virus

Due to contamination of poliovirus vaccine

No proof indicating etiology in tumors
Polyomavirus:

- genome structure
- envelope?
- prevalence
- initial replication where?
- persists where?
Circular

dsDNA

Ubiquitous and persistant

Respiratory tract

Kidney
What are the functions of each strand for polyomavirus?
One strand encodes early T (transforming) antigens.

Other strand encodes late structural genes (capsid proteins VP1 - VP3)
Polyomavirus is typically acquired ___________ before the age of ________.
Asymptomatically

15
Describe the spread of polyomavirus in the human body.
1. Inoculation of respiratory tract
(multiplies there too)

2. Primary viremia

3. Goes to kidneys
(multiplies there)

4. Transient secondary viremia

If IMMUNOCOMPETENT:
latent indefinitely in kidney

If IMMUNODEFICIENT:
reactivation of virus

BK goes to urinary tract and multiplies

JC goes to CNS
In immunodeficient patients, BK virus multiplication in the urinary tract can cause what diseases? x2
Viruria

Hemorrhagic cystitis
In immunodeficient patients, JC virus can cause what in the CNS?
PML
(Progressive Multifocal Leukoencephalopathy)
Clinically for polyomavirus:

- symptoms of primary infection
- can be reactivated during what event?
Asymptomatic

pregnancy
In 40% of immunocompromised patients with polyomavirus, the actual virus can be detected in what?
Urine
What are the BK virus related diseases associated with transplants? x2
Ureteral stenosis in renal patients

Hemorrhagic cystitis in bone marrow transplants.
What is the disease associated with JC virus?
PML
(Progressive Multifocal Leukoencephalopathy)
PML:

- caused by what virus?
- most common population group?
- physiological effect of disease
- involved cells
- histological revelations
- symptoms x4
- mortality
JV virus of polyomavirus

AIDS patients (~10%)

Subacute demyelinating disease

Oligodendrocytes

Multiple foci of white matter in frontal/parietal/temporal lobes

Impaired speech
Impaired mentation
Impaired vision
Paralysis

90% death
What are the diseases associated with the KI virus?
None associated YET!!!!
T/F - KI virus can be detected in urine.

T/F - KI virus can be detected in blood.
Both false.

Detected by PCR:
(1% in nasopharyngeal aspirates)
(0.5% in fecal samples)
How do you diagnose polyomavirus infection? x3
PCR in:

- CSF (JCV, PML)
- Urine (JCV, BKV)

FISH in biopsy (JCV, PML)

Urine cytological tests
(enlarged cells with dense, basophilic intranuclear inclusions similar to CMV-induced inclusions)
Treatment for Polyomavirus infections.
None.

Just alleviate immune suppression.